Figure 8

Schematic diagram of the cellular response to Sindbis vector infection. Sindbis vector replication forms double-stranded RNA species, which activate PKR. PKR is able to inhibit cellular translation through eIF2α phosphorylation and the formation of stress granules. Translation inhibition blocks the production of new Mcl-1, which is rapidly turned over. The remaining Mcl-1, in complex with Bak, is displaced by BH3 only protein Bik, thus releasing Bak. Downstream of PKR, JNK is activated, which causes the release of Bad from its complex with 14-3-3. Bad translocates to the mitochondria and disrupts the complex between Bcl-xl and Bak. Bak oligomerizes resulting in the release of cytochrome c from the mitochondria. Caspase 9 is cleaved causing caspase 3 cleavage and downstream apoptosis.